Curcumin induces apoptosis and inhibits proliferation in infantile hemangioma endothelial cells via downregulation of MCL-1 and HIF-1α

Abstract

Background:Curcumin has been used as an alternative medicine for the treatment of infantile hemangiomas (IHs); however, the mechanism underlying the effectiveness of curcumin in IHs remains largely unclear.Methods:In this study, we isolated primary human hemangioma endothelial cells (HemECs) from fresh surgical specimens of 3 patients. We treated HemECs by curcumin and investigated the alterations in proliferative and apoptotic signaling pathways with cell counting kit-8, flow cytometry, western blotting, immunofluorescence, and real-time polymerase chain reaction.Results and Conclusion:We found that curcumin potently inhibited proliferation in HemECs, achieving low-micromolar IC50 (the half maximal inhibitory concentration) value. We also observed that treatment with curcumin induced apoptosis in HemECs, as evidenced by positively Annexin-V-FITC staining, caspase-3 activation, and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP) in the treated cells. Moreover, we showed that curcumin suppressed the expression of antiapoptotic protein myeloid cell leukemia-1 (MCL-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF).Altogether, our study suggests that the effectiveness of curcumin in IHs may be associated with its potent antiproliferative and apoptotic activities in HemECs.

Silencing long non‑coding RNA NEAT1 suppresses the tumorigenesis of infantile hemangioma by competitively binding miR‑33a‑5p to stimulate HIF1α/NF‑κB pathway

“…HiF1α is significantly upregulated in proliferating IH tissues compared with involuting iH tissues, and an in vitro study indicated that hypoxia upregulated HiF1α expression in hemangioma stem cells (26). curcumin-mediated HiF1α downregulation inhibits cell proliferation and induces infantile hemangioma endothelial cell apoptosis (18). The results of the present study suggested that HiF1α was highly expressed in iH tissues, and the expression levels of HiF1α in proliferating iH tissues were higher compared with involuting iH tissues.…”

“…Hypoxia-inducible factor 1α (HIF1α) is a crucial regulator during hypoxia-induced angiogenesis, but it is also involved in the growth of hemangiomas ( 16 , 17 ). Curcumin-mediated downregulation of HIF1α inhibits the proliferation of human hemangioma endothelial cells (HemECs) ( 18 ). Furthermore, by using starBase, NEAT1 was predicted as a ceRNA that regulates HIF1α by sponging miR-33a-5p ( 19 ).…”

Lauryl Gallate Induces Apoptotic Cell Death through Caspase-dependent Pathway in U87 Human Glioblastoma CellsIn Vitro

“…Numerous studies have shown that HIF-1α inhibition induces apoptosis in many cancer cell lines, including glioblastoma (42,43). Furthermore, previous studies have reported that downregulation of MCL-1 and HIF-1α is implicated in curcumin-mediated apoptosis in infantile hemangioma endothelial cells (44). AKT is also involved in cell survival (45,46); It is activated by phosphorylation (47) and, herein, it was shown that LG inhibited the expression of p-AKT ( Figure 4B).…”

Vulvar Hemangioma: Case Report

“…[12][13][14] More recent reports also suggest alternative modalities for the treatment of this disease, such as the use of curcumin, indicating that the effectiveness of curcumin in hemangioma may be associated with its potent antiproliferative and apoptotic activities in hemangioma endothelial cells. 15…”